Chronic neutropenia. A new canine model induced by human granulocyte colony-stimulating factor.

W P Hammond; E Csiba; A Canin; H Hockman; L M Souza; J E Layton; D C Dale

doi:10.1172/JCI115049

Department of Medicine, University of Washington School of Medicine, Seattle 98195.

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Department of Medicine, University of Washington School of Medicine, Seattle 98195.

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Department of Medicine, University of Washington School of Medicine, Seattle 98195.

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Department of Medicine, University of Washington School of Medicine, Seattle 98195.

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Department of Medicine, University of Washington School of Medicine, Seattle 98195.

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Department of Medicine, University of Washington School of Medicine, Seattle 98195.

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Department of Medicine, University of Washington School of Medicine, Seattle 98195.

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Published in Volume 87, Issue 2 on February 1, 1991
J Clin Invest. 1991;87(2):704–710. https://doi.org/10.1172/JCI115049.
© 1991 The American Society for Clinical Investigation

Published February 1, 1991 - Version history

Normal dogs were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) at 10 micrograms/kg/day for 30 d, which caused an initial neutrophilia, followed by a prolonged period of chronic neutropenia. A control dog treated with recombinant canine G-CSF (rcG-CSF) showed persistent neutrophilia over 3 mo. Serum from dogs during neutropenia contained an antibody to rhG-CSF, which neutralized the stimulatory effects of both rhG-CSF and rcG-CSF on dog marrow neutrophilic progenitor cell growth and on NFS-60 cell proliferation. 4 mo after discontinuation of rhG-CSF, the dogs' neutrophil counts returned to the normal range. Rechallenge with the rhG-CSF re-induced severe neutropenia in 1 wk. Neutropenia was transferred by plasma infusion from a neutropenic dog to a previously normal dog. These data suggest that human rhG-CSF immunizes normal dogs and thereby induces neutralization of endogenous canine G-CSF and neutropenia. This model system should allow more precise definition of the in vivo role of G-CSF.